The objectives of the proposed research are to define the anticonvulsant properties of marihuana and surrogates, to evaluate the potential of cannabinoids as antiepileptic drugs, to determine if marihuana produces a "rebound" CNS hyperexcitability which may increase seizure susceptibility in epileptic patients, to assess whether marihuana can potentially jeopardize the effectiveness of antiepileptic drugs, and to study the metabolism and fate of delta 9-THC in the body. The anticonvulsant activity and the effect on excitability and seizure susceptibility will be studied in acutely and chronically treated rats and mice by a variety of electroshock and pentylenetetrazole tests. The results of these studies will provide comparative data with clinically useful antiepileptic drugs. The drug interaction aspect will be investigated by determining whether marihuana alters the anticonvulsant activity of antiepileptics such as diphenylhydantoin and phenobarbital. The metabolism and the fate will be studied with H3-delta 9-THC and thin layer chromatography. The purpose of these experiments is to identify the active substance or substances by correlating plasma, CSF, and brain levels with anticonvulsant activity. BIBLIOGRAPHIC REFERENCES: Karler, R., W. Cely, and S. A. Turkanis. Anticonvulsant activity of delta 9 tetrahydrocannabinol and its 11-hydroxy and 8 alpha, 11-dihydroxy metabolites in the frog. Res. Commun. Chem. Pathol. Pharmacol. 9:441-452, 1974. Turkanis, S. A., and R. Karler. Influence of anticonvulsant cannabinoids on posttetanic potentiation at isolated bullfrog ganglia. Life Sci. 17:569-578, 1975.